Metabolic Pathway Alignment Based on Similarity between Chemical Structures

Abstract

In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Metabolic pathways are formed as the products of these reactions are used as the substrates of other reactions. Comparative analyses of the metabolic pathways among species provide important information on both evolution and potential pharmacological targets. Here, we propose a method to align the metabolic pathways based on similarities between chemical structures. To measure the degree of chemical similarity, we formalized a scoring system using the MACCS keys and the Tanimoto/Jaccard coefficients. To determine the effectiveness of our method, it was applied to analyses of metabolic pathways in Escherichia coli. The results revealed compound similarities between fructose and mannose biosynthesis and galactose biosynthesis pathways.

SubMAP: Aligning Metabolic Pathways with Subnetwork Mappings

“…The first type considers one pathway at a time and explores its important properties such as its robustness (Edwards and Palsson, 2000), steady states (Devloo et al, 2003;Garg et al, 2007;Ay et al, 2009b), modular structure (Lu et al, 2006;Schuster et al, 2002;Ay et al, 2010), network motifs (Milo et al, 298;Wernicke and Rasche, 2006;Grochow and Kellis, 2007), as well as its representation (Michal, 1998;Babur et al, 2010). The second type is the comparative approach which considers multiple pathways to identify their frequent subgraphs (Koyuturk et al, 2004;Qian and Yoon, 2009) and their alignments (Singh et al, 2008(Singh et al, , 2007Liao et al, 2009;Kalaev et al, 2008;Sharan et al, 2005;Kalaev et al, 2009;Dost et al, 2007;Flannick et al, 2006;Koyuturk et al, 2005;Pinter et al, 2005;Berg and Lassig, 2004;Dandekar et al, 1999;Tohsato and Nishimura, 2008;Tohsato et al, 2000;Cheng et al, 2009;Ay et al, 2008Ay et al, , 2009a. Alignment is a fundamental type of comparative analysis that aims to identify similar parts between pathways.…”

Consistent Alignment of Metabolic Pathways Without Abstraction

“…In order to reduce the time complexity of the alignment, some existing algorithms restrict the topology of query pathways 6,7 . For instance, the method proposed by Tohsato et al 7 works for only non-cyclic pathways, whereas the algorithm of Pinter et al 8 restricts the query pathways to multi-source trees.…”

“…For instance, the method proposed by Tohsato et al 7 works for only non-cyclic pathways, whereas the algorithm of Pinter et al 8 restricts the query pathways to multi-source trees. However, those restrictions are far from the reality and they limit the applicability of the methods to only a small percentage of pathways.…”

“…Due to the discrepancies in the EC hierarchy, the accuracy of this method is questionable. In 2007, they proposed another method 7 , which only considers chemical structures of compounds for alignment. This idea, however, totally ignores the effect of other entities such as enzymes and reactions.…”

Metabolic pathway prediction based on inclusive relation between cyclic substructures

“…There are several approaches for pathway prediction such as fingerprints (Tohsato and Nishimura 2008), reaction rule-base (Langowski and Long 2002;Talafous et al 1994;Ellis et al 2006;Hou et al 2004;Oh et al 2007) and maximum common subgraph search (MCSS) (Kotera et al 2008). The fingerprint-based approach predefines some important molecular fragments and determines which fragments are included in each metabolite as bit-strings consisting of 0's and 1's.…”